Marijuana and memory impairment: Effect on free recall and recognition memory

The effect of marijuana on memory was evaluated by presenting two groups of 17 male volunteers with lists of repeated or nonrepeated words following administration of a single marijuana cigarette containing 14 mg Δ⁹-THC. An immediate free recall, final free recall and recognition memory test followed. Results indicated that marijuana significantly decreased immediate and final free recall but only slightly influenced recognition memory. Rate of acquisition on the repeated lists was the same for both groups. Long term retention of encoded information was not influenced by marijuana. The shape of the serial position curves departed slightly from those reported by other investigators in that some effects of the drug on the recency portion of the curve were noted. Both internal and external intrusions were elevated under marijuana.     

Drugs and human memory: effects of low doses of nitrazepam and hyoscine on retention.

1 The effects of diazepam (5 mg) and hyoscine hydrobromide (0.3 mg) were assessed in two memory tasks: short-term retention of digit strings and the free recall of items from categorizable lists. 2 One hundred and two healthy subjects were tested in an independent-groups design. Subjects were assigned randomly to either placebo, diazepam or hyoscine groups. Treatments were administered orally under double-blind conditions. 3 The short-term retention of digits was impaired to an equivalent degree and locus for both drugs (P less than 0.05). This effect was ascribed to the action on primary memory. 4 The drugs produced no significant effects on the recall of categorizable lists either in terms of the number of words recalled or the cohesiveness of categorical recall. 5 These results demonstrate that drugs of different pharmacological actions produce isomorphic psychological deficits in memory and that 'anti-memory' effects on one task should not be extrapolated to all aspects of memory.     

Effects of repeated doses of fluvoxamine,mianserin and placebo on memory and measures of sedation

The effects on memory and learning of fluvoxamine 50 mg twice a day were compared with those of mianserin 20 mg twice a day and placebo, each given for 8 days in a double-blind cross-over design to nine healthy human volunteers. At least 1 week was left between the 8-day courses of drugs. Subjects were given a learning task (three trial recall of categorisable word lists) before and 3.5 h after a morning dose on day 1 and before their morning dose on day 8. Delayed recall was assessed on days 1, 4 and 8.Fluvoxamine had no effect on memory performance. Mianserin reduced learning and recall after a single dose but had no effect on day 8 of treatment. The single dose of mianserin had no retrograde effect on memory, affected primacy and middle position items but not recency in the serial position curve, and was seen in reduced inter-trial subjective organisation of recall. Subjects' performance on the first trial of the memory task correlated significantly with their performance on a simple reaction time task, with finger tapping speeds and with their subjective ratings of alertness. It was concluded that the impairments of memory produced by one dose of mianserin are partially by-products of the sedative effects of the drug. Tolerance to both memory impairments and sedative effects built up over the 8-day treatment of mianserin. Offprint requests to: H.V. Curran     

Retrograde enhancement by alcohol of delayed free recall performance

Two experiments are reported in which retrograde enhancement of human memory by alcohol was observed. In both studies male undergraduate volunteers performed an immediate free recall task before and after consuming either alcohol (0.66 abs alc/kg) or placebo. About two hours later, many words as they could delayed free recall was tested when subjects were asked to write down as many words as they could remember from the free recall trials in the session. Subjects given alcohol recalled significantly more words from lists heard before drinking than subjects given placebo; this effect appeared more pronounced for words from the primacy portion of the lists. The possibility that this retrograde enhancement effect is due to alcohol's effects on brain reward systems is raised.     

Effects of post-trial administration of nicotine on human memory: evaluating the conditions for improving memory

In the studies reported here, we investigated the effects of nicotine on memory for unrelated word lists. Nicotine was delivered through cigarette smoking, and memory performance was assessed using both intentional and incidental recall tasks, and employing an additional, indirect measure of memory. We report the results of four experiments in which we manipulated 1) the intake of nicotine using nicotine-containing and nicotine-free cigarettes, 2) the associative aspects of the word-sets, by unrelated words and category words and by instructing subjects to use an associative mnemonic strategy, 3) the opportunity for rehearsal between the presentation and recall, and 4) the time of nicotine administration, post- or pre-trial. We found a positive effect of post-trial nicotine on memory in the incidental recall task, as indicated by enhanced repetition priming, but no effect of nicotine on either immediate recall or pronunciation times (experiments 1 and 2). In experiment 3 we examined the effects of post-trial nicotine using associative and unrelated word-lists, when volunteers were instructed to use an associative mnemonic strategy. We found no main effect of nicotine, but when volunteers were distracted from rehearsal, related words were recalled better than unrelated words. Experiment 4 was a positive control for the timing of nicotine administration within our experimental design, and this showed that pre-trial nicotine not only improved free recall but differentially enhanced the recall of category words over unrelated words. We conclude that nicotine does modulate memory, that associative aspects of verbal memory in particular are sensitive to modulation by nicotine, and that the effects are more reliably observed with pre-trial than with post-trial administration. The conditions under which post-trial effects can be observed remain unclear.     

Distinguishing between attentional and amnestic effects in information processing: the separate and combined effects of scopolamine and nicotine on verbal free recall

An important issue in our understanding of cholinergic modulation of information processing is the extent to which drug-induced changes affect memory processes per se or simply the attentional processes required for effective acquisition of information. In this study, we examined the separate and combined effects of scopolamine and nicotine on verbal free recall. A single dose of nicotine improved recall performance on supraspan lists (30 words), but not on short lists (10 words). The same dose of nicotine had no effect on the scopolamine-induced recall deficits observed for both 30 and 10 word lists. The results are discussed in terms of the independence of attention and memory processes and the specificity of action of these two cholinergic compounds.     

Effects of diazepam and scopolamine on storage,retrieval and organizational processes in memory

The effects of intramuscular injections of diazepam (0.3 mg/kg) and scopolamine (8 g/kg) on memory processes and subjective moods were studied in 36 volunteers. Subjects (Ss) were tested in groups of four in a double blind procedure with treatments distributed according to a Latin square design. Lists of words were presented to Ss who were then tested with an immediate free recall test prior to drug administration. Following injection delayed free recall and recognition tests were given. Subsequently two sets of lists were presented separately and tested in the same fashion. Two of the lists in the last set were composed of words falling into distinct categories. Memory was additionally analyzed by testing immediate recall of digit sequences and employing a visual recognition test. Subjective moods were evaluated with a rating questionnaire.Both diazepam and scopolamine impaired memory functions although the action of the latter drug was more pronounced and prolonged. The deficit appeared to be in the storage process leaving retrieval processes unaffected. Scopolamine in addition interfered with organizational processes. Subjectively, scopolamine also produced a larger sedative effect than diazepam.     

Dose-response analysis of the behavioral effects of diazepam: I. Learning and memory

A total of 120 healthy volunteers were randomly assigned to four treatments (placebo, 0.1, 0.2, and 0.3 mg/kg) and three testing times (7 AM, 1 PM and 7 PM). Immediate and delayed free recall of word lists revealed consistent decreases in performance as oral diazepam dose increased from 0.1, 0.2, to 0.3 mg/kg. Paradoxically, as the dose increased, the number of predrug list words recalled also increased. A serial number-learning task displayed a pattern of delayed improvement of acquisition as the dose increased. Response times in a semantic-categories task were prolonged as the dose increased. Parallel recovery functions were observed for all doses and tasks. Full recovery after a single administration of 0.1, 0.2, and 0.3 mg/kg doses was estimated to occur after 3.5, 4.5, and 5.5 h, respectively. Several analyses were consistent with the view that acquisition and not retrieval was impaired by diazepam. There were no circadian interactions with the effects of the drug.     

Marijuana: Effects on storage and retrieval of prose material

In a two phase design, an attempt was made to differentiate the effect of marijuana on the storage and retrieval of prose material. In the first phase, 40 male subjects were administered a single 500 mg marijuana cigarette containing 2.1% ⁹-TCH or a placebo cigarette. Fifteen minutes after smoking, they listened to and at the same time read a narrative passage of approximately 200 words in length. Subsequently, an immediate free recall test was given in which subjects were required to write down as much of the story as they could remember. The second phase was conducted 24 h later. Marijuana and placebo subjects were randomly subdivided into four groups with half of the subjects participating in the same drug condition as occurred on day one while the others switched drug state. Fifteen minutes after smoking, all subjects recalled the passage pressented on day one and then were given 24 questions concerning facts and events in the story which could be answered in a few words. These questions served as retrieval cues. Following this, a new passage was presented in the same manner as occurred on day one. After an immediate free recall test, another cued recall test was administered.Results indicated that marijuana reduced immediate recall under both cued and uncued conditions in comparison to placebo. No relative cued recall advantage was found in the marijuana groups for the old or new story and marijuana produced only a moderate decrement in recall of the old story on day two. However, marijuana given in the second phase significantly reduced memory for items recalled in the initial phase irrespective of drug or cueing condition in phase one, suggesting that retrieval was also affected. Some decrement in recall of the new story did occur as a function of drug state change in group M-P. This effect was related to the serial position of input items. Serial position did not interact with drug state under any other recall condition.     

Primacy and recency effects in rhesus monkeys (Macaca mulatta) using a serial probe recognition task I. Effects of diazepam

In this study, we evaluated the effects of diazepam (0.2, 0.8, 1.6 and 3.2 mg/kg; IM) on the primacy and recency memory effects in four rhesus monkeys trained on a six-item serial probe recognition (SPR) task. Only the highest dose of diazepam (3.2 mg/kg) consistently affected the shape of the monkeys' serial position curves. Accuracy on the probe trials was disrupted for list items which occurred in the middle portion and recency memory component of the serial position curve, without affecting the primacy component. Diazepam, however, also produced several nonspecific effects on SPR performance. Both the 1.6 and 3.2 mg/kg diazepam doses disrupted accuracy on the non-matching probe trials, and the 3.2 mg/kg dose caused an increase in response latencies which were unrelated to any one component of the serial position curve. This is the first demonstration in nonhuman primates showing that the primacy and recency memory effects can be differentiated on the basis of diazepam dose.The opinions and assertions contained in this report are the private views of the author and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. In conducting the research described in this report, the investigators adhered to the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals, NIH Publication No. 86-23     

Temazepam impairs effortful but not automatic processing of stimulus elements

The experiment investigated the effects in healthy volunteers of a single dose of temazepam (30 mg, oral) on effortful and automatic processing, by measuring memory for information and its context. Effortful processing was impaired, as shown by significant impairments in free recall of an 18-item list, but automatic processing was spared, as evidenced by no impairments in recall of the frequency of presentation, the colour, size or form of the items. In a second task, temazepam significantly impaired both recognition and recency memory of 30 items, although these scores were not correlated. Temazepam caused significant sedation, measured by an objective test and by subjective ratings, but this did not correlate with the memory impairments. The pattern of results is discussed with reference to the hypothesis that the memory impairments resulting from benzodiazepines are due to a reduction in information processing resources and thus affect effortful processing more than automatic processing.     

The effects and interactions of scopolamine, physostigmine and methamphetamine on human memory.

Seventy college age subjects learned and recalled a series of word lists prior to being injected with methamphetamine (0.2 mg/kg or 0.3 mg/kg), scopolamine (8 microgram/kg), or a placebo. Following the injection subjects were tested for their free recall and recognition of the words and they completed a short-term digit recall task. Subjects who had previously received scopolamine were next injected with either methamphetamine (0.2 mg/kg or 0.3 mg/kg), physostigmine (32 microgram/kg), or placebo, while other subjects received a placebo injection. The above memory procedure was then repeated with a second series of word lists. In addition, subjective feelings were measured with a questionnaire. Scopolamine and methamphetamine did not affect recall of information learned prior to injection. Scopolamine did, however, impair performance in both the digit recall task and in the second series of memory tests. Physostigmine and methamphetamine alleviated most of the memory deficits and sedation produced by scopolamine. Methamphetamine alone produced subjective arousal and a small improvement in recall of words learned after injection and a large increase in incorrect responding.     

Immediate free recall of drug names: effects of similarity and availability.

The prescribing frequency, subjective familiarity, and two measures of similarity as predictors of error in immediate free recall of drug names were assessed. The study design utilized prospective, computer-based, word memory experiments in which 30 pharmacists and 66 college students were asked to immediately recall 15 lists of three three-syllable drug names. Intralist similarity was systematically varied. The number of words forgotten or incorrectly recalled was then examined as a function of similarity, subjective familiarity, and prescribing frequency. The primary outcome measure was the number of item errors in free recall. Pharmacists made fewer errors than college students. Familiarity reliably enhanced item recall among both pharmacists and college students. Prescribing frequency enhanced recall among both pharmacists and college students except when college students recalled generic names. Orthographic (i.e., spelling) similarity was reliably associated with item recall in both groups. Fewer errors were made when lists were more orthographically similar. Among pharmacists, there was an inverted U-shaped relationship between phonologic (i.e., sound) similarity and item errors, with the fewest errors being made on the most similar lists. Among college students, phonologic similarity was not reliably associated with item errors. Frequently prescribed and subjectively familiar drug names are more accurately recalled than rarely prescribed and unfamiliar names. Orthographically similar lists of drug names are easier to recall than dissimilar lists because similarity provides cues that facilitate the retrieval of degraded short-term memories. The effects of similarity, familiarity, and frequency on short-term memory of drug names vary as a function of task and stimulus characteristics.     

Alprazolam and lorazepam effects on memory acquisition and retrieval processes

A double-blind study involving healthy young adult males examined acute effects of two benzodiazepines (alprazolam 1 mg and lorazepam 2 mg) on long-term memory acquisition and retrieval, using Buschke's "selective reminding" task and a free recall task. Subjects learned lists consisting of high and low imagery nouns. The assessments, done at baseline and hourly for 4 hours after drug ingestion, also included two psychomotor tests and subjective ratings by subjects. Both benzodiazepines produced marked memory impairment. Contrary to the prevailing view that benzodiazepines primarily impair long-term memory acquisition rather than retrieval, results from Buschke's task indicated impairment of retrieval as well. This finding may be related to the procedures and assumptions of Buschke's task. The benzodiazepine-induced impairments increased over the course of successive trials on the same list. Both drugs decreased the normal superiority in recall of high imagery words relative to low imagery words, impaired psychomotor performance, and increased subjective sedation. Alprazolam and lorazepam produced equally intense impairments. Alprazolam tended to produce earlier impairment and earlier recovery.     

Marijuana: an analysis of storage and retrieval deficits in memory with the technique of restricted remiding

A simple word list learning technique which has previously been shown to be useful clinically in evaluating disordered memory in organic patients, was employed to assess the effects of marijuana on storage and retrieval processes in memory. Twelve male subjects were administered marijuana and placebo in two separate sessions separated by a one week interval. Each subject served as his own drug control. Fifteen min after smoking a 500 mg marijuana cigarette containing 2.1% Δ⁹ - THC or a placebo cigarette, each subject presented with a 30-item word list and then required to recall it in writing. Half of the subjects in the first session recalled one list while the other half recalled a second similarly constructed list. The lists were reversed during the second session. Following the initial recall test, onlythose words not recalled were presented again. Presentation of a given word continued only until an item was recalled once. There were 12 recall trials. This method termed restricted reminding allows for the simultaneous evaluation of storage and retrieval without confounding due to continuous presentation. The critical data were the number of items recalled without presentation following initial recall. Results indicated that marijuana produced a slower rate of acquisition of items into storage in comparison to placebo although the same number of items were eventually stored under both conditions. The drug appeared to exert its most deleterious effect on the retrieval of information from long term storage.     

The effect of alcohol and repetition at encoding on implicit and explicit false memories

Rationale Alcohol impairs explicit memory, whilst leaving implicit memory relatively intact. Less is known about its effects on false memories.Aim The present study examines the effects of alcohol on explicit and implicit false memories using study list repetition as a tool for modulating learning at encoding.Methods Thirty-two participants were given either an alcohol (0.6 g/kg) or placebo beverage before undergoing an encoding phase consisting of 10 lists of nine associated words (veridical items). Each list was associated to a word, which was not presented at encoding (semantically associated non-studied lure; critical item), serving as the measure for false memory. Half of the lists were presented once, and half were repeated three times. The next day, participants underwent an implicit (stem completion and post hoc awareness measurements), and an explicit (free recall) task.Results Alcohol decreased veridical and false explicit memory for singularly presented lists compared to placebo; no group difference existed for repeated lists. Implicit veridical memory was not affected by alcohol. Awareness memory measures demonstrated in placebo participants an increased ability with repetition in rejecting false memories. The reverse was found in intoxicated participants who with repetition accepted more false memories.Conclusion Alcohol appears to decrease semantic activation leading to a decline in false memories. Increased learning with repetition, which increases the rejection of false memories under placebo, is reversed under alcohol leading to a decrease in rejection of false memories. The latter effect of alcohol may be due to its ability to impair monitoring processes established at encoding.     

Conditions under which lorazepam can facilitate retrieval.

Memory is composed of three stages: acquisition, consolidation, and retrieval. By impairing acquisition processes, benzodiazepines cause anterograde amnesia while leaving intact information learned before the drug was taken. In some circumstances, retrieval of this information is even improved by benzodiazepines. It has been hypothesized that this phenomenon is not a true facilitation of retrieval processes, but is the result of reduced interference from items presented after drug administration and is thus a secondary consequence of drug-induced amnesia. Experiment 1 investigated the effect of 0.5, 1, and 2.5 mg of lorazepam on explicit episodic memory in healthy young volunteers. The 1-mg dose was found to significantly improve recall of items presented before drug administration without causing amnesia for items presented after drug administration, thus excluding an interference explanation. Experiment 2 investigated the conditions necessary to obtain facilitated retrieval with 1 mg of lorazepam. The results showed that facilitation was found only when two lists of semantically related material were presented, but that both of the lists could be presented before drug administration, thus excluding an effect of lorazepam on consolidation. Facilitation could be demonstrated in both direct (free recall) and indirect (backwards reading) retrieval tasks and when all of the material was presented after lorazepam administration. This improved retrieval could therefore be of clinical relevance, but any benefits would be reduced at higher doses that at the same time impair acquisition of new information. However, because 1 mg of lorazepam is an effective anxiolytic dose, these results suggest that it is possible to combine effective anxiety reduction with some benefits to memory.     

Using a computer model to explore impairments of acquisition processes following ingestion of diazepam

Hypotheses about the information processes impaired in diazepam-induced amnesia were tested by fitting the output from a computer simulation of list learning to observed serial position curves and to overt rehearsal protocols. Twenty-four subjects received an average weight-relative dosage of 0.18 mg/kg oral diazepam; 24 subjects received placebo. Immediate free recall of 16-word lists was examined at 2- and 8-s presentation times. Subjects receiving diazepam recalled significantly fewer words than placebo subjects (diazepam=6.77 ± 2.39 words; placebo=9.29 ± 1.42 words); their memory impairment was greater at the 8-s than 2-s presentation time. Tests of nonlinear regression models based on computer simulations of list learning performance were consistent with the hypothesis that diazepam reduces rehearsal capacity and disrupts the formation or utilization of contextual and inter-item associations. Among these causes of diazepam-induced amnesia, the disruption of contextual associations appears most important. The results further suggest that quantitative modeling of memory data may complement traditional methods of inferring relationships between brain processes and cognitive dysfunction in amnesic states.Bold letters represent model parameters     

Effects of tryptophan depletion on brain potential correlates of episodic memory retrieval

RATIONALE: Neuropsychological impairments in depressive illness may be secondary to proposed serotonergic abnormalities. Acute tryptophan depletion (ATD) in healthy subjects impairs episodic memory, but the mechanism of this is unclear. OBJECTIVES: To examine the effects of ATD on the neural correlates of episodic memory retrieval in healthy subjects. METHODS: Fourteen healthy men were given an amino acid cocktail drink with or without tryptophan, in a double blind, crossover design. Event related potentials (ERPs) were recorded during a well-validated episodic memory task performed 5 h after drink ingestion. Subjects listened to words spoken in a male or female voice. At test, old and new words were presented visually; subjects judged whether words were old or new, and if old, the gender of the voice at study. RESULTS: ATD led to an 84+/-5% reduction in plasma free tryptophan concentrations, and significantly impaired episodic memory recall. ERP recordings demonstrated previously reported left parietal and right frontal "old/new" differences for ERPs to items associated with accurate episodic memory retrieval versus correctly rejected new items. ATD increased ERP voltage between 500 and 1400 ms post-stimulus particularly over posterior regions of the scalp, but there was no interaction with item type. Topographical analysis of the old/new difference revealed no significant treatment by site interaction. CONCLUSIONS: ATD impairs episodic memory recall with no effect on the magnitude or topography of the neural correlates of retrieval in healthy subjects. This suggests that the effects of ATD on recall may reflect an impairment of memory encoding and/or consolidation.     

Effortful processing is a requirement for nicotine-induced improvements in memory

 We report two studies examining the effects of nicotine on memory in minimally deprived smokers. In experiment 1, semantically related words were recalled significantly better than unrelated words following nicotine, even when volunteers were explicitly instructed to target the unrelated word set for recall. Experiment 2 examined the effect of nicotine on two different types of lexical association: association by joint category membership (semantically related items), and association by derived meaning (”encapsulated” word pairs). Nicotine-induced improvements in recall were observed only for category associates and not for encapsulated word pairs. This implies that explicit, effortful processing of material in the presence of nicotine is necessary for improved recall performance to be observed. Received: 15 October 1997 / Final version: 13 November 1997